EP0491438B1 - Contraceptive regimen - Google Patents
Contraceptive regimen Download PDFInfo
- Publication number
- EP0491438B1 EP0491438B1 EP91203282A EP91203282A EP0491438B1 EP 0491438 B1 EP0491438 B1 EP 0491438B1 EP 91203282 A EP91203282 A EP 91203282A EP 91203282 A EP91203282 A EP 91203282A EP 0491438 B1 EP0491438 B1 EP 0491438B1
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- Prior art keywords
- dosage units
- estrogen
- dosage
- progestagen
- equivalent
- Prior art date
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
Definitions
- the invention relates generally to contraceptive preparations, and more specifically to an oral contraceptive regimen.
- Known oral contraceptive regimens typically involve administering tablets containing a combination of estrogen and progestogen to an adult female over her menstrual cycle, usually followed by a "pill-free" or blank pill period.
- the amount of progestogen in the tablets of these regimens typically increases during the administration of the regimen. Alternatively, the amount of progestogen may remain fixed, or reaches a peak and then declines.
- a progestogen is administered from at least the fifth day to the twenty-fifth day of the menstrual cycle, the dosage of the progestogen being greater during the last seven days of administration than it is during the first seven days.
- German Patent Application No. 3,229,612 to Syntex (USA) Inc. describes a contraceptive regimen wherein the amount of progestogen administered peaks at mid-cycle, but then decreases.
- U. S. Patent No. 4,292,315 to Vorys describes another contraceptive regimen having a mid-menstrual cycle peak of progestogen and then subsequently declines.
- no exogenous steroids are administered during the first 7 days.
- the tablets administered may contain only a progestogen (e.g. 0.35 milligrams ("mg") of norethindrone).
- mg milligrams
- tablets containing both an estrogen and the progestogen e.g. 0.35 mg of norethindrone
- tablets containing both an estrogen and a progestogen e.g.
- norethindrone acetate which is approximately twice as potent as norethindrone
- tablets are administered in which the amount of estrogen and progestogen are at half the daily dosage of the preceding 7 tablets (e.g. 0.35 mg norethindrone).
- Canadian Patent Application No. 2,000,438 to Akzo, nv describes a multiphasic oral contraceptive preparation containing a progestogen and an estrogen in a first phase, and a progestogen only in the second phase.
- the amount of progestogen in the second phase is less than that in the last dosage unit of the first phase.
- the first phase may be split-up into three sub-phases, each successive sub-phase having more progestogen than the one earlier.
- the invention thus includes a multiphasic combination and contraceptive kit containing from 21 to 24 daily sequential dosage units.
- the 21 dosage units are divided into three phases.
- the first phase contains 6 to 8 first dosage units, each containing a progestogen at a dosage equivalent in progestogenic activity to 75 to 150 micrograms (" ⁇ g") desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20-25 ⁇ g ethinyl estradiol.
- the second phase contains 6 to 8, preferably 7, each containing less progestogen than in the first dosage units, but still having progestogen in a dosage equivalent in progestogenic activity to 75 to 125 ⁇ g desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20 ⁇ g ethinyl estradiol.
- the third phase contains 6 to 8 third dosage units, each containing less progestogen than in the earlier dosage units, but still containing a progestogen at a dosage equivalent in progestogenic activity 75 to 100 ⁇ g desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20 ⁇ g ethinyl estradiol.
- the kit may also include a fourth phase of 4 to 7 fourth dosage units having no contraceptive steroids.
- the invention also includes a pharmaceutical product (i.e. the birth control pack containing the dosage unit regimen), and a process of manufacturing this pharmaceutical product.
- a pharmaceutical product i.e. the birth control pack containing the dosage unit regimen
- Preferred progestogens for use with the invention include 3-ketodesogestrel ("etonogestrel”), desogestrel, levonorgestrel, norgestrel, gestodene, and other compounds with similar progestogenic activity. Especially preferred are 3-ketodesogestrel and desogestrel.
- levo-norgestrel, desogestrel, and 3-keto-desogestrel are relatively equipotent, when administered orally, in progestogenic activity.
- Gestodene is approximately 1.5 times as potent as these compounds orally.
- Norgestrel is about one-half as potent as levo-norgestrel.
- Each phase preferably contains seven dosage units.
- 125 ⁇ g of desogestrel or 3-ketodesogestrel are preferably used.
- 100 ⁇ g of desogestrel or 3-keto-desogestrel are preferably used.
- 75 ⁇ g of desogestrel or 3-ketodesogestrel are preferably used.
- Examples of preferred estrogens include 17 ⁇ -estradiol and ethinyl estradiol.
- Mestranol and 17- ⁇ -ethinyl estradiol 3-methylether are also useful estrogens.
- 1 mg of 17 ⁇ -estradiol is equivalent in estrogenic activity to 0.015 mg of ethinyl estradiol and 0.030 mg of mestranol.
- the estrogen and progestogen are incorporated into dosage units for oral administration.
- dosage unit generally refers to physically discrete units suitable as unitary dosages for humans or animals, each containing a predetermined quantity of active material (e.g. estrogen or progestogen) calculated to produce the desired effect.
- active material e.g. estrogen or progestogen
- dosage units e.g. tablets
- conventional additives e.g. fillers, colorants, polymeric binders and the like
- any pharmaceutically acceptable additive which does not interfere with the function of the active compounds can be used in the one or more of the compositions.
- Suitable carriers with which the compositions can be administered include lactose, starch, cellulose derivatives and the like used in suitable amounts. Lactose is a preferred carrier. Mixtures of carriers can also be used.
- a process of manufacturing the pharmaceutical product according to the invention preferably involves incorporating the desired dosages of contraceptive steroid (i.e. progestogen and estrogen) into a tablet by known techniques.
- Tablets containing different amounts and types of contraceptive steroids may be of different colors, and kept in different portions of, for example, a blister pack.
- the package containing the dosage units will preferably contain 21 or 28 dosage units arranged sequentially therein. Preferably there will be 28 dosage units, of which seven will be blanks.
- a method of contraception using the invention comprises administering, either enterally or parenterally, to a female of child-bearing age:
- a preferred method of contraception using the invention comprises orally administering to a female:
- the regimen may be repeated for as long as contraception is desired.
- These methods might also include administering blank dosage units during the first seven days.
- One or more dosage units may contain an iron salt (e.g. 75 mg of ferrous fumarate) if desired.
- This regimen is effective and can be used with a relatively low amount of contraceptive steroids.
- compositions of tablets are Compositions of tablets:
- compositions of tablets are Compositions of tablets:
- compositions of tablets are Compositions of tablets:
- compositions of tablets are Compositions of tablets:
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- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Orthopedics, Nursing, And Contraception (AREA)
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Abstract
Description
- Technical Field. The invention relates generally to contraceptive preparations, and more specifically to an oral contraceptive regimen.
- Background Art. Known oral contraceptive regimens typically involve administering tablets containing a combination of estrogen and progestogen to an adult female over her menstrual cycle, usually followed by a "pill-free" or blank pill period. The amount of progestogen in the tablets of these regimens typically increases during the administration of the regimen. Alternatively, the amount of progestogen may remain fixed, or reaches a peak and then declines.
- For example in French Patent Application No. 2,223,018 to Ortho Pharmaceutical, a progestogen is administered from at least the fifth day to the twenty-fifth day of the menstrual cycle, the dosage of the progestogen being greater during the last seven days of administration than it is during the first seven days.
- Another example of an oral contraceptive regimen which increases the amount of progestogen throughout the woman's menstrual cycle is described in European Patent Application No. 36,229 to Akzo, nv.
- In Belgian Patent No. 892,801 to Syntex (USA) Inc., a method of treating menopause is described also involving an increase in the amount of progestogen administered during the regimen's cycle.
- German Patent Application No. 3,229,612 to Syntex (USA) Inc. describes a contraceptive regimen wherein the amount of progestogen administered peaks at mid-cycle, but then decreases.
- U. S. Patent No. 4,292,315 to Vorys describes another contraceptive regimen having a mid-menstrual cycle peak of progestogen and then subsequently declines. In this regimen, during the first 7 days, no exogenous steroids are administered. During days 8 to 14, the tablets administered may contain only a progestogen (e.g. 0.35 milligrams ("mg") of norethindrone). During days 15 to 18, tablets containing both an estrogen and the progestogen (e.g. 0.35 mg of norethindrone) are administered. During days 19 to 25, tablets containing both an estrogen and a progestogen (e.g. 1.0 mg of norethindrone acetate, which is approximately twice as potent as norethindrone) are administered. Finally during days 26 to 28, tablets are administered in which the amount of estrogen and progestogen are at half the daily dosage of the preceding 7 tablets (e.g. 0.35 mg norethindrone).
- Canadian Patent Application No. 2,000,438 to Akzo, nv describes a multiphasic oral contraceptive preparation containing a progestogen and an estrogen in a first phase, and a progestogen only in the second phase. The amount of progestogen in the second phase is less than that in the last dosage unit of the first phase. The first phase may be split-up into three sub-phases, each successive sub-phase having more progestogen than the one earlier.
- It is found that by initially starting with a high amount of progestogen - after the usual 7 day pill-free or blank period - then gradually tapering the progestogen dosage over the contraceptive regimen, an effective oral contraceptive regimen results having a relatively lower amount of contraceptive steroids.
- The invention thus includes a multiphasic combination and contraceptive kit containing from 21 to 24 daily sequential dosage units. The 21 dosage units are divided into three phases. The first phase contains 6 to 8 first dosage units, each containing a progestogen at a dosage equivalent in progestogenic activity to 75 to 150 micrograms ("µg") desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20-25 µg ethinyl estradiol. The second phase contains 6 to 8, preferably 7, each containing less progestogen than in the first dosage units, but still having progestogen in a dosage equivalent in progestogenic activity to 75 to 125 µg desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20 µg ethinyl estradiol. The third phase contains 6 to 8 third dosage units, each containing less progestogen than in the earlier dosage units, but still containing a progestogen at a dosage equivalent in progestogenic activity 75 to 100 µg desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20 µg ethinyl estradiol.
- The kit may also include a fourth phase of 4 to 7 fourth dosage units having no contraceptive steroids.
- The invention also includes a pharmaceutical product (i.e. the birth control pack containing the dosage unit regimen), and a process of manufacturing this pharmaceutical product.
- Preferred progestogens for use with the invention include 3-ketodesogestrel ("etonogestrel"), desogestrel, levonorgestrel, norgestrel, gestodene, and other compounds with similar progestogenic activity. Especially preferred are 3-ketodesogestrel and desogestrel. As an approximation, levo-norgestrel, desogestrel, and 3-keto-desogestrel are relatively equipotent, when administered orally, in progestogenic activity. Gestodene is approximately 1.5 times as potent as these compounds orally. Norgestrel is about one-half as potent as levo-norgestrel.
- Each phase preferably contains seven dosage units. In the first dosage units, 125 µg of desogestrel or 3-ketodesogestrel are preferably used. In the second dosage units, 100 µg of desogestrel or 3-keto-desogestrel are preferably used. In the third dosage units, 75 µg of desogestrel or 3-ketodesogestrel are preferably used.
- Examples of preferred estrogens include 17β-estradiol and ethinyl estradiol. Mestranol and 17-α-ethinyl estradiol 3-methylether are also useful estrogens. As an approximation and when administered orally, 1 mg of 17β-estradiol is equivalent in estrogenic activity to 0.015 mg of ethinyl estradiol and 0.030 mg of mestranol.
- The estrogen and progestogen ("contraceptive steroids"), or either of them are incorporated into dosage units for oral administration. The term "dosage unit" generally refers to physically discrete units suitable as unitary dosages for humans or animals, each containing a predetermined quantity of active material (e.g. estrogen or progestogen) calculated to produce the desired effect.
- Conventional techniques may be used to make dosage units according to the invention. Conventional methods and compositions for making such dosage units are well-known to those skilled in the art. For example, methods and compositions for making tablets and pills, containing active ingredients, are described in the standard reference, Chase et al., Remington's Pharmaceutical Sciences, (16th ed., Mack Publishing Co., Easton. PA, U.S.A., 1980) ("Remington's"), at pages 1553 through 1584. Methods of making powders, and their composition are described at pages 1535 through 1552 of the reference. Methods of coating pharmaceutical dosage forms are described at pages 1585 to 1593 of Remington's.
- For making dosage units, e.g. tablets, the use of conventional additives, e.g. fillers, colorants, polymeric binders and the like is contemplated. In general any pharmaceutically acceptable additive which does not interfere with the function of the active compounds can be used in the one or more of the compositions.
- Suitable carriers with which the compositions can be administered include lactose, starch, cellulose derivatives and the like used in suitable amounts. Lactose is a preferred carrier. Mixtures of carriers can also be used.
- A process of manufacturing the pharmaceutical product according to the invention preferably involves incorporating the desired dosages of contraceptive steroid (i.e. progestogen and estrogen) into a tablet by known techniques. Tablets containing different amounts and types of contraceptive steroids may be of different colors, and kept in different portions of, for example, a blister pack. The package containing the dosage units will preferably contain 21 or 28 dosage units arranged sequentially therein. Preferably there will be 28 dosage units, of which seven will be blanks.
- A method of contraception using the invention comprises administering, either enterally or parenterally, to a female of child-bearing age:
- a) no contraceptive steroids for the first 7 days;
- b) a progestogen at a daily dosage equivalent in progestogenic activity to 75 to 150 µg desogestrel administered orally, and an estrogen at a daily dosage equivalent in estrogenic activity to 20-25 µg ethinyl estradiol administered orally for the next 6 to 8 days;
- c) a progestogen at a daily dosage equivalent in progestogenic activity to 75 to 125 µg desogestrel administered orally, but in an amount less than that administered during the prior 6 to 8 days, and an estrogen at a daily dosage equivalent in estrogenic activity to 20 µg ethinyl estradiol administered orally for the next 6 to 8 days; and
- d) a progestogen at a daily dosage equivalent in progestogenic activity 75 to 100 µg desogestrel administered orally, but in an amount less than that administered during the prior 6 to 8 days, and an estrogen at a daily dosage equivalent in estrogenic activity to 20 µg ethinyl estradiol administered orally for the last 7 days.
- A preferred method of contraception using the invention comprises orally administering to a female:
- a) for the first 7 days, no dosage units at all;
- b) for the next 7 days, first dosage units containing a progestogen at a daily dosage equivalent in progestogenic activity to 75 to 150 µg desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20-25 µg ethinyl estradiol;
- c) for the next 7 days, second dosage units containing less progestogen than in the first dosage units, but still having a progestogen at a daily dosage equivalent in progestogenic activity to 75 to 125 µg desogestrel and an estrogen at a daily dosage equivalent in estrogenic activity to 20 µg ethinyl estradiol; and
- d) for the last 7 days, third dosage units containing less progestogen than in the second dosage units, but still containing a progestogen at a daily dosage equivalent in progestogenic activity 75 to 100 µg desogestrel and an estrogen at a daily dosage equivalent in estrogenic activity to 20 µg ethinyl estradiol.
- After the completion of one cycle of the regimen, the regimen may be repeated for as long as contraception is desired. These methods might also include administering blank dosage units during the first seven days. One or more dosage units may contain an iron salt (e.g. 75 mg of ferrous fumarate) if desired.
- This regimen is effective and can be used with a relatively low amount of contraceptive steroids.
- The invention is further explained by the following illustrative EXAMPLES.
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Compound Amount (mg/tablet) ethinyl estradiol 0.020 desogestrel 0.125 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) ethinyl estradiol 0.020 desogestrel 0.100 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) ethinyl estradiol 0.020 desogestrel 0.075 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) ethinyl estradiol 0.020 3-ketodesogestrel 0.125 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) ethinyl estradiol 0.020 3-ketodesogestrel 0.100 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) ethinyl estradiol 0.020 3-ketodesogestrel 0.075 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) micronized(17β)estradiol 2.000 desogestrel 0.125 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) micronized estradiol 2.000 desogestrel 0.100 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) micronized estradiol 2.000 desogestrel 0.075 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) ethinyl estradiol 0.025 desogestrel 0.150 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) ethinyl estradiol 0.020 desogestrel 0.125 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 -
Compound Amount (mg/tablet) ethinyl estradiol 0.020 desogestrel 0.100 potato starch 6.500 povidone 1.950 stearic acid 0.650 colloidal silicone dioxide 0.650 dl-α-tocopherol 0.080 lactose qsad 65.000 - Reference herein to specific embodiments or examples should not be interpreted as limitations to the scope of the invention, which is defined by the appended claims.
Claims (9)
- A method of manufacturing of a multiphasic combination and contraceptive kit comprising a package containing 21 to 24 daily sequential dosage units of:
a first phase of 6 to 8 first dosage units, said first dosage units each containing a progestagen at a dosage equivalent in progestagenic activity to 75 to 150 micrograms desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20 to 25 micrograms ethinyl estradiol;
a second phase of 6 to 8 second dosage units, said second dosage units each containing less progestagen than in the first dosage units, but still having a progestagen at a dosage equivalent in progestagenic activity to 75 to 125 micrograms desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20 micrograms ethinyl estradiol; and
a third phase of 6 to 8 third dosage units, said third dosage units each containing less progestagen than in the second dosage units, but still containing a progestagen at a dosage equivalent in progestagenic activity to 75 to 100 micrograms desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20 micrograms ethinyl estradiol, comprising:
mixing predetermined quantities of progestagen with predetermined quantities of estrogen and converting said mixture into first dosage units;
mixing predetermined quantities of progestagen with predetermined quantities of estrogen and converting said mixture into second dosage units; and
mixing predetermined quantities of progestagen with predetermined quantities of estrogen and converting said mixture into third dosage units. - The method of manufacturing of the multiphasic combination and contraceptive kit according to claim 1 wherein the kit further comprises a fourth phase of 4 to 7 fourth dosage units containing no contraceptive steroids.
- The method of manufacturing of the multiphasic combination and contraceptive kit according to claim 1 or claim 2 wherein said progestagen is selected from the group consisting of 3-ketodesogestrel, desogestrel, levo-norgestrel, gestodene, and mixtures thereof.
- The method of manufacturing of the multiphasic combination and contraceptive kit according to claim 3 wherein the progestagen in all phases containing a progestagen is desogestrel or 3-ketodesogestrel.
- The method of manufacturing of the multiphasic combination and contraceptive kit according to claim 1, claim 2, claim 3, or claim 4 wherein said estrogen is selected from the group consisting of 17β-estradiol, ethinyl estradiol, mestranol, 17-α-ethinyl estradiol 3-methylether, and mixtures thereof.
- The method of manufacturing of the multiphasic combination and contraceptive kit acording to claim 5 wherein the estrogen administered in all phases containing an estrogen is 17β-estradiol or ethinyl estradiol.
- A method of manufacturing of a multiphasic combination and contraceptive kit comprising a package containing 24 daily sequential dosage units of:
a first phase of 8 first dosage units, each containing a progestagen at a dosage equivalent in progestagenic activity to 150 µg desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 25 µg ethinyl estradiol;
a second phase of 8 second dosage units, each containing a progestagen at a dosage equivalent in progestagenic activity to 125 µg desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20 µg ethinyl estradiol; and
a third phase of 8 third dosage units, each containing a progestagen at a dosage equivalent in progestagenic activity to 100 µg desogestrel and an estrogen at a dosage equivalent in estrogenic activity to 20 µg ethinyl estradiol, comprising:
mixing predetermined quantities of progestagen with predetermined quantities of estrogen and converting said mixture into first dosage units;
mixing predetermined quantities of progestagen with predetermined quantities of estrogen and converting said mixture into second dosage units; and
mixing predetermined quantities of progestagen with predetermined quantities of estrogen and converting said mixture into third dosage units. - A method of manufacturing of a multiphasic combination and contraceptive kit containing sequential phases of dosage units having progestagen and estrogen characterized in that the amount of progestagen contained in the dosage units of each phase of the kit decreases incrementally along with the phase, comprising:
mixing predetermined quantities of progestagen with predetermined quantities of estrogen and converting said mixture into first dosage units;
mixing predetermined quantities of progestagen with predetermined quantities of estrogen and converting said mixture into second dosage units; and
mixing predetermined quantities of progestagen with predetermined quantities of estrogen and converting said mixture into third dosage units.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP90203372 | 1990-12-17 | ||
EP90203372 | 1990-12-17 |
Publications (2)
Publication Number | Publication Date |
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EP0491438A1 EP0491438A1 (en) | 1992-06-24 |
EP0491438B1 true EP0491438B1 (en) | 1996-04-03 |
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ID=8205204
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP91203282A Expired - Lifetime EP0491438B1 (en) | 1990-12-17 | 1991-12-12 | Contraceptive regimen |
Country Status (18)
Country | Link |
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US (1) | US5418228A (en) |
EP (1) | EP0491438B1 (en) |
JP (1) | JPH04290830A (en) |
KR (1) | KR100186780B1 (en) |
CN (1) | CN1036833C (en) |
AT (1) | ATE136219T1 (en) |
AU (1) | AU645637B2 (en) |
CA (1) | CA2057747C (en) |
DE (1) | DE69118494T2 (en) |
DK (1) | DK0491438T3 (en) |
ES (1) | ES2087965T3 (en) |
FI (1) | FI98985C (en) |
GR (1) | GR3020181T3 (en) |
IE (1) | IE62665B1 (en) |
NO (1) | NO179311C (en) |
NZ (1) | NZ240970A (en) |
PT (1) | PT99819B (en) |
ZA (1) | ZA919770B (en) |
Families Citing this family (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4227989A1 (en) * | 1992-08-21 | 1994-06-09 | Schering Ag | Agent for transdermal application containing 3-keto-desogestrel |
US6407082B1 (en) * | 1996-09-13 | 2002-06-18 | New Life Pharmaceuticals Inc. | Prevention of ovarian cancer by administration of a vitamin D compound |
DE4344462C2 (en) * | 1993-12-22 | 1996-02-01 | Schering Ag | Composition for contraception |
DK0782449T3 (en) * | 1994-09-22 | 2003-08-04 | Akzo Nobel Nv | Process for preparing dosage units by wet granulation |
IL115445A (en) * | 1994-10-17 | 1999-08-17 | Akzo Nobel Nv | Solid pharmaceutical compositions comprising low dosage active ingredient oil and excipient capable of binding water and their preparation |
DE19540253C2 (en) * | 1995-10-28 | 1998-06-04 | Jenapharm Gmbh | Multi-phase preparation for contraception based on natural estrogens |
US5747480A (en) * | 1996-05-08 | 1998-05-05 | American Home Products Corporation | Oral contraceptive |
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1991
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- 1991-12-12 EP EP91203282A patent/EP0491438B1/en not_active Expired - Lifetime
- 1991-12-12 ES ES91203282T patent/ES2087965T3/en not_active Expired - Lifetime
- 1991-12-12 AT AT91203282T patent/ATE136219T1/en not_active IP Right Cessation
- 1991-12-13 AU AU89679/91A patent/AU645637B2/en not_active Ceased
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CN1036833C (en) | 1997-12-31 |
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NO914969D0 (en) | 1991-12-16 |
FI98985C (en) | 1997-09-25 |
DE69118494D1 (en) | 1996-05-09 |
NZ240970A (en) | 1994-05-26 |
FI915914A0 (en) | 1991-12-16 |
FI915914A (en) | 1992-06-18 |
KR920011515A (en) | 1992-07-24 |
IE62665B1 (en) | 1995-02-22 |
ATE136219T1 (en) | 1996-04-15 |
GR3020181T3 (en) | 1996-09-30 |
DK0491438T3 (en) | 1996-07-08 |
PT99819A (en) | 1992-12-31 |
NO179311B (en) | 1996-06-10 |
IE914272A1 (en) | 1992-06-17 |
AU645637B2 (en) | 1994-01-20 |
NO179311C (en) | 1996-09-18 |
PT99819B (en) | 2001-05-31 |
CN1062464A (en) | 1992-07-08 |
ES2087965T3 (en) | 1996-08-01 |
AU8967991A (en) | 1992-06-18 |
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